Cells can be damaged by exposure to ultrasound. For example, ultrasound can cause irreversible cell damage and induce destructive cell membrane modifications. Several reports have suggested that cavitation resulting from the collapse of gas bubbles generated by acoustic pressure fields may be the cause for cell damage following ultrasonic irradiation. It has also been suggested that cavitation induces single-strand breaks in DNA by the action of residual hydrogen peroxide.
The use of ultrasound in cancer therapy has become an important issue. Ultrasound has been used in conjunction with hyperthermia, and photo-, radio-, and chemotherapy. Malignant cells are known to be more susceptible to these combined methods than their normal counterparts. The effect of direct irradiation (e.g., ultrasound, laser, light) on certain molecules (e.g., classical photosensitizers and sonosensitizers) is the generation of highly active oxygen species such as singlet oxygen, superoxide radicals, hydroperoxides, or fatty acid radicals, which can play an important role in cancer treatment, acting selectively on malignant cells.
According to the origin of the radiation, the above-described therapy is termed PDT (photodynamic therapy) or, if by ultrasound or sonoluminescence: SDT (sonodynamic therapy). Addition of a photosensitizer is a pre-requisite for both therapies. While the general effects induced by SDT and PDT are different in terms of cell viability, both SDT (specifically related to the ultrasonic cavitational activity) and PDT generate active oxygenated species and lead to a diminution of the intracellular thiol levels. In the case of PDT by ultraviolet-A (UVA), apoptosis of T helper cells can be induced by the generation of singlet oxygen, but this effect depends essentially on the initial concentration in photosensitizers (PS) and on the local oxygen concentration. For SDT, as a result of the high energies involved, the cell lysis is the major phenomenon, probably masking other effects on the surviving cells.
U.S. Pat. No. 4,971,991 to Umemura et al. discloses the use of ultrasound to treat tumor cells, but relies on high ultrasound power levels, and does not describe the use of microbubbles. Other patents describing ultrasound and microbubbles, such as U.S. Pat. No. 5,215,680 to D'Arrigo, rely on the use of the cavitational and thermal effects of ultrasound to treat tumors, as opposed to individual cancer cells, the extent of which is determined by duration and number of treatments. This type of treatment uses high power and long irradiation times, predominantly producing cell lysis and necrosis. See Kondo, Cancer Letters 178(1), 63-70, (2002).